MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma.
MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma.
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MicroRNA-550a 在肝细胞癌中充当促转移基因并直接靶向细胞质多聚腺苷酸化元件结合蛋白 4
DOI：
10.1371/journal.pone.0048958
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Tian Q;Liang L;Ding J;Zha R;Shi H;Wang Q;Huang S;Guo W;Ge C;Chen T;Li J;He X
MicroRNA（miRNAs）是一类小的非编码RNA分子，通常在染色体断裂点处发现，并在人类癌症中起着至关重要的作用。我们的前期研究发现miR-550a在肝细胞癌（HCC）中表达上调，miR-550a是一种在7p14.3上频繁扩增的miRNA。然而，miR-550a在HCC中的可能功能和分子机制尚不清楚。在这项研究中，功能获得和功能丧失分析显示，miR-550 a显著促进HCC细胞迁移和侵袭。此外，我们发现胞质多聚腺苷酸化元件结合蛋白4（CPEB 4）是HCC中miR-550 a的潜在靶点。进一步的分析表明，CPEB 4表达的敲低显著促进HCC细胞的迁移和侵袭，这与miR-550 a对HCC细胞的作用表型相似。此外，CPEB4表达的降低介导了miR-550 a诱导的肝癌细胞迁移和侵袭。有趣的是，CPEB 4在HCC中经常下调，其表达水平与HCC患者的总生存率相关。总之，这些结果表明，这种新鉴定的miR-550a-CPEB 4轴可能参与HCC细胞转移。此外，CPEB 4的表达水平可用于预测HCC患者的预后。我们的研究结果为HCC的治疗和预后提供了新的潜在靶点。
MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that are often found at chromosomal breakpoints and play a vital role in human cancer. Our previous study found that miR-550a, a frequently amplified miRNA on 7p14.3, was upregulated in hepatocellular carcinoma (HCC). However, the possible functions and molecular mechanisms of miR-550a in HCC remain unknown. In this study, gain-of-function and loss-of-function assays revealed that miR-550a markedly promoted HCC cell migration and invasion. In addition, we discovered that cytoplasmic polyadenylation element binding protein 4 (CPEB4) was a potential target of miR-550a in HCC. Further analyses showed that knockdown of CPEB4 expression significantly facilitated HCC cell migration and invasion, which phenocopied the effects of miR-550a on HCC cells. Moreover, a decrease in CPEB4 expression mediated miR-550a-induced liver cancer cell migration and invasion. Interestingly, CPEB4 is frequently downregulated in HCC, and its expression levels correlate with the overall survival of HCC patients. Together, these results suggested that this newly identified miR-550a-CPEB4 axis may be involved in HCC cell metastasis. Moreover, the expression levels of CPEB4 could be used to predict outcomes in HCC patients. Our findings provide novel potential targets for HCC therapy and prognosis.
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影响因子：
11.4
作者：
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通讯作者：
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影响因子：
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